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    GENE:

    DNMT3A (DNA methyltransferase 1)

    i
    Other names: DNMT3A, DNA Methyltransferase 3 Alpha, DNA (Cytosine-5-)-Methyltransferase 3 Alpha, DNA (Cytosine-5)-Methyltransferase 3A, DNA MTase HsaIIIA, DNA Cytosine Methyltransferase 3A2, DNA Methyltransferase HsaIIIA, DNMT3A2, Dnmt3a
    2d
    Integration of genomic and clinical variables improves the prediction of myelodysplastic syndromes to acute myeloid leukaemia transformation and prognosis. (PubMed, Br J Haematol)
    This work provides the first genomic characterisation of a diagnosed MDS cohort in China and establishes the first risk prediction model for MDS-to-AML transformation, alongside novel prognostic models for OS and PFS. These tools offer improved prognostic prediction and potential guidance for therapeutic strategies in Chinese patients with MDS.
    Journal
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    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • NF1 (Neurofibromin 1) • JAK2 (Janus kinase 2) • SF3B1 (Splicing Factor 3b Subunit 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • ETV6 (ETS Variant Transcription Factor 6) • SRSF2 (Serine and arginine rich splicing factor 2) • BCOR (BCL6 Corepressor) • CSF3R (Colony Stimulating Factor 3 Receptor) • STAT3 (Signal Transducer And Activator Of Transcription 3) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • STAG2 (Stromal Antigen 2) • GATA2 (GATA Binding Protein 2) • CALR (Calreticulin)
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    TP53 mutation • SRSF2 mutation • STAT3 mutation
    2d
    Nodal T-follicular helper cell lymphoma with hodgkin/reed-sternberg-like cells: Clinicopathologic and molecular characterization of 11 cases. (PubMed, Pathol Res Pract)
    AITL with HRS-like cells is prone to misdiagnosis as CHL due to overlapping morphological and immunophenotypic features. Integration of EBER, TCR/IG clonality assessment, and molecular profiling, particularly the identification of TET2 and RHOA mutations is essential for accurate classification. Recognizing this entity is critical for avoiding diagnostic pitfalls and guiding appropriate therapeutic strategies.
    Journal • PD(L)-1 Biomarker • IO biomarker
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    DNMT3A (DNA methyltransferase 1) • PD-1 (Programmed cell death 1) • TNFRSF8 (TNF Receptor Superfamily Member 8) • BCL6 (B-cell CLL/lymphoma 6) • TET2 (Tet Methylcytosine Dioxygenase 2) • KMT2D (Lysine Methyltransferase 2D) • CREBBP (CREB binding protein) • PAX5 (Paired Box 5) • CD4 (CD4 Molecule) • CXCL13 (Chemokine (C-X-C motif) ligand 13) • ICOS (Inducible T Cell Costimulator) • RHOA (Ras homolog family member A) • MME (Membrane Metalloendopeptidase) • BRD4 (Bromodomain Containing 4)
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    TET2 mutation • TNFRSF8 positive • TNFRSF8 expression
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    CART-30
    3d
    Proteostasis Stress Drives Stem Cell Aging, Clonal Hematopoiesis and Leukemia. (PubMed, bioRxiv)
    Together, these findings reveal proteostasis as a key constraint in the aging hematopoietic system that imposes a selective bottleneck. Hsf1 activation enables both physiological adaptation in aging stem cells and pathological clonal outgrowth in pre-leukemic and leukemic states, establishing proteostasis control as a pivotal mechanism linking stem cell aging to clonal hematopoiesis and malignancy.
    Journal
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    NRAS (Neuroblastoma RAS viral oncogene homolog) • DNMT3A (DNA methyltransferase 1) • HSF1 (Heat Shock Transcription Factor 1)
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    NRAS mutation
    4d
    The Prognostic Value of Integrating Copy Number Alteration Profiles in NPM1-Mutated Acute Myeloid Leukemia: An Exploratory Study. (PubMed, Appl Clin Genet)
    This exploratory study suggests that combining CNAs and gene mutation profiles may potentially improve the existing prognostic evaluation system for NPM1-mutated AML patients. Confirmation of these results requires additional validation in larger prospective cohorts.
    Journal
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    FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • TET2 (Tet Methylcytosine Dioxygenase 2)
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    FLT3-ITD mutation • NPM1 mutation
    5d
    Retrospective study on the clinical outcomes and characteristics of acute myeloid leukemia: different outcomes in the same risk group. (PubMed, PeerJ)
    Idarubicin, cytarabine, etoposide (IA ± E) chemotherapy yielded superior survival, while azacitidine+venetoclax (AZA+VEN) regimens underperformed. The study was registered on the Chinese clinical trial registry (ChiCTR) platform (No. ChiCTR2500096484).
    Clinical data • Retrospective data • Journal
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    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • CEBPA (CCAAT Enhancer Binding Protein Alpha)
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    TP53 mutation • FLT3 mutation • NPM1 mutation • KIT mutation • TET2 mutation
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    Venclexta (venetoclax) • cytarabine • azacitidine • etoposide IV • idarubicin hydrochloride
    5d
    FLT3-ITD with NPM1 and/or DNMT3A co-mutations in acute myeloid leukemia: prognostic significance and the role of maintenance therapy post-transplantation. (PubMed, Blood Sci)
    In conclusion, FLT3-ITD-based double or triple mutations showed comparable posttransplant outcomes. FLT3-ITD MRD status and early maintenance therapy were key prognostic and therapeutic factors.
    Journal
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    FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1)
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    FLT3-ITD mutation • NPM1 mutation
    9d
    Using genomics to refine pediatric AML risk stratification. (PubMed, Hematology Am Soc Hematol Educ Program)
    Key issues ahead include identifying which genetic features truly affect outcomes, using this information to personalize therapy, predicting who will benefit from targeted drugs, and choosing the best markers to track disease response over time. Looking forward, collaborative efforts are urgently needed to validate pediatric-specific biomarkers, test novel drug combinations, and link genetic data to clinical outcomes to design trials and future treatment strategies.
    Review • Journal • IO biomarker
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    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • BCL2 (B-cell CLL/lymphoma 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • KMT2A (Lysine Methyltransferase 2A) • WT1 (WT1 Transcription Factor) • NUP98 (Nucleoporin 98 And 96 Precursor 2) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • CBFA2T3 (CBFA2/RUNX1 Partner Transcriptional Co-Repressor 3) • GLIS2 (GLIS Family Zinc Finger 2)
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    TP53 mutation • KMT2A rearrangement
    10d
    Frequency and impact of somatic co-occurring mutations on post-transplant outcomes in acute myeloid leukemia: a multicenter registry analysis on behalf of the EBMT ALWP. (PubMed, Bone Marrow Transplant)
    OS was additionally negatively affected when the ten genes were unmutated. Notably, outcomes were excellent for SAR mutations (2-year LFS 76%, OS 84%), indicating allo-HCT in CR1 can overcome their adverse risk at diagnosis.
    Journal
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    TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NPM1 (Nucleophosmin 1) • DNMT3A (DNA methyltransferase 1) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • SRSF2 (Serine and arginine rich splicing factor 2)
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    TP53 mutation • FLT3-ITD mutation • NPM1 mutation • RUNX1 mutation • ASXL1 mutation • TET2 mutation • SRSF2 mutation
    13d
    Targeted methylation of cg24067911 suppresses colorectal cancer metastasis through BCL6-ATXN1-CDH1 axis. (PubMed, Oncogene)
    Furthermore, ATXN1 was found to act as a transcription factor that upregulates CDH2, promoting epithelial-mesenchymal transition and facilitating CRC metastasis. These findings not only reveal that cg24067911 methylation modulates CRC metastasis through a novel epigenetic mechanism involving ATXN1 and CDH2, but also highlight cg24067911 as a potential prognostic marker for CRC and suggest that targeted epigenetic therapies could be an effective strategy for treating CRC metastasis in the future.
    Journal
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    DNMT3A (DNA methyltransferase 1) • BCL6 (B-cell CLL/lymphoma 6) • CDH1 (Cadherin 1) • CDH2 (Cadherin 2)
    15d
    TMEM91::TAL1 Fusion gene in a middle-aged female with rapid MDS to secondary AML progression: a case report. (PubMed, Hematology)
    Despite multiple cycles of azacitidine, within one month, the patient had transitioned into sAML with blasts increased to 55% with heterogeneity in the sample, and TMEM91::TAL1 expression increased to 2.83%...This case illustrates the value of comprehensive molecular profiling, including RNA-seq, in cases of rapidly progressive MDS that cannot be diagnosed through standard molecular diagnostics. The temporal relationship between expression of the fusions and disease progression warrants additional studies of TMEM91::TAL1 in myeloid malignancies.
    Journal
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    DNMT3A (DNA methyltransferase 1) • TAL1 (TAL BHLH Transcription Factor 1)
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    azacitidine
    17d
    Integrated Genomic and Transcriptomic Profiling of Isolated Trisomies in AML Reveals Cell Cycle Dysregulation and Therapeutic Vulnerabilities. (PubMed, J Cell Mol Med)
    Drug sensitivity profiling revealed subgroup-specific vulnerabilities: IT-8 to DNA damage checkpoint inhibitors, IT-21 to PLK/mTOR inhibitors and IT-13+22 to BRAF/EGFR-targeted agents. These findings highlight AML-IT heterogeneity and therapeutic potential.
    Journal
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    BRAF (B-raf proto-oncogene) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • IL6 (Interleukin 6) • TNFA (Tumor Necrosis Factor-Alpha) • CALR (Calreticulin) • HSPA5 (Heat Shock Protein Family A (Hsp70) Member 5) • MCM4 (Minichromosome Maintenance Complex Component 4) • CDC25A (Cell Division Cycle 25A) • CDC7 (Cell Division Cycle 7) • GNRP (Ras-Specific Guanine Nucleotide-Releasing Factor 1) • HSP90AB1 (Heat Shock Protein 90 Alpha Family Class B Member 1)